{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T05:58:48Z","timestamp":1792475928469,"version":"4.5.0"},"reference-count":20,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,12]]},"abstract":"<jats:p content-type=\"fine-print\"><jats:italic>Object.<\/jats:italic> Mitogen-activated protein kinase (MAPK) may be involved in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage. This study was conducted to investigate the ability of the MAPK inhibitors PD98059 and U-0126 to reverse vasospasm in a double-hemorrhage model in dogs.<\/jats:p><jats:p content-type=\"fine-print\"><jats:italic>Methods.<\/jats:italic> Twenty-two adult mongrel dogs of either sex, each weighing 18 to 24 kg, were divided randomly into four groups: control SAH (four dogs), vehicle- (dimethyl sulfoxide, six dogs), PD-98059\u2014 (six dogs), and U-0126\u2014treated groups (six dogs). The double-hemorrhage model was created by an autologous blood injection into the cisterna magna on Days 0 and 2. An intracisternal injection of MAPK inhibitors was administered once per day on Days 3 through 6. Cerebral angiography was performed on Days 0 and 7 before the animals were killed. Western blot analysis was used to study the effects of hemorrhage and drug treatment on the MAPK immunoprecipitation.<\/jats:p><jats:p content-type=\"fine-print\">Severe vasospasm developed in the dogs in the control and vehicle-treated groups (basilar artery [BA] diameter reduction 46.6 \u00b1 5.5% and 49.3 \u00b1 4.6%, respectively). In the PD-98059\u2014treated group, most of the dogs developed mild vasospasm (18.9 \u00b1 6.2%). In the U-0126\u2014treated group, severe vasospasm was observed despite treatment (39.6 \u00b1 6.4%). The PD-98059 but not the U-0126 abolished MAPK immunoprecipitation in the spastic BAs. However, treatment with either PD-98059 or U-0126 improved the clinical scores of the dogs.<\/jats:p><jats:p content-type=\"fine-print\"><jats:italic>Conclusions.<\/jats:italic> The present study is the first in which the effects of MAPK inhibitors on vasospasm have been investigated in vivo. The authors demonstrate that MAPK may play a role in vasospasm and that PD-98059 is a potential candidate for the treatment of cerebral vasospasm.<\/jats:p>","DOI":"10.3171\/jns.2000.93.6.1041","type":"journal-article","created":{"date-parts":[[2009,5,13]],"date-time":"2009-05-13T17:27:02Z","timestamp":1242235622000},"page":"1041-1047","source":"Crossref","is-referenced-by-count":39,"title":["Effects of MAPK inhibitors on cerebral vasospasm in a dog double hemorrhage 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